Intensive research in bio-engineering has been conducted in the search for flexible biomaterials that could support cell growth and cells attachment. Flexible synthetic materials that support cell growth without the aid of synthetic extracellular matrix proteins are still rare. Cholesteryl liquid crystal containing cholesteryl moieties may have suitable biological affinity. Human keratinocytes (HaCat) were cultured with a nematic liquid crystal and three cholesteryl liquid crystals of different formulation. Subsequently, the trypan blue dye exclusion assay was used to determine cell viability in the liquid crystals. The two classes of liquid crystal were characterized by Differential Scanning Calorimeter (DSC) and polarizing microscope (POM) to understand the nature of the interface material. The cell viability study in medium containing liquid crystals verified that liquid crystals had no effects on cell viability. However, only the surface of cholesteryl liquid crystal has shown affinity to HaCat cells. In addition, cells continued to proliferate in the presence of liquid crystals without a change of medium for eight days. No sign of exothermic and endothermic activities at 370C were observed from the DSC test results for the three samples. Biological and mechanical test result of the cholesteryl liquid crystals has shown that cholesteryl liquid crystals are non toxic and support cell attachment without extracellular matrix protein at very low elasticity.

The multicomponent ternary complex of 4-dimethylaminobenzoic acid (4-DABA), 3,5-dinitrobenzoic acid
(3,5-DNBA), and 4,40-bipyridine (BIPY) has been studied by variable temperature X-ray and neutron diffraction. Proton disorder is
observed within the 4-DABA homodimers present and quantitatively evaluated from neutron data. The effect of the crystal
environment and in particular the pyramidalization of the nitrogen atom within the 4-DABA molecule and the consequential
effect on the presence of hydrogen atom disorder are discussed with reference to the previously determined pure 4-DABA
structure and the binary cocrystal with 3,5-DNBA.

Experimental solubilities of budesonide, hydrocortisone, and prednisolone in ethanol + water mixtures at 298.2
K are reported. The solubility of drugs was increased with the addition of ethanol and reached the maximum
values of the volume fractions of 90 %, 80 %, and 80 % of ethanol. The Jouyban-Acree model was used to fit
the experimental data, and the solubilities were reproduced using previously trained versions of the Jouyban-Acree
model and the solubility data in monosolvents in which the overall mean relative deviations (OMRDs) of the
models were 5.1 %, 6.4 %, 37.7 %, and 35.9 %, respectively, for the fitted model, the trained version for ethanol
+ water mixtures, and generally trained versions for various organic solvents + water mixtures. Solubilities
were also predicted by a previously established log-linear model of Yalkowsky with the OMRD of 53.8 %.

Of particular importance in recent years has been the development
of techniques for producing nanoparticles (NPs) of
poorly-water soluble drugs with dimensions less than 1000 nm
for which their high surface area can lead to improvements
in bioavailability. Furthermore, the small size of these particles
can also enable cellular uptake, particularly for positively charged systems. Therefore, an overall objective of this part
of the project was to produce nanoparticles with different
levels of positive surface charge using the bottom-up method.

Crystallisation is a widely used technique for purification and
manipulation of the final crystal form of therapeutic agents.
In particular, potential exists to control the mechanical properties
of ibuprofen through control of crystal habit. The aim
of this study was therefore to understand the influence of
crystallisation conditions on the morphology of ibuprofen to
enable production of crystals with different habits.

Co-crystal screening is routinely undertaken using high-throughput solution growth. We report a low- to medium throughput
approach, encompassing both a melt and solution crystallization step as a route to the identification of co-crystals. Prior
to solution studies, a melt growth step was included utilizing the Kofler mixed fusion method. This method allowed elucidation of
the thermodynamic landscape within the binary phase diagram and was found to increase overall screening efficiency. The
pharmaceutically acceptable adduct nicotinamide was selected and screened against a small set of active pharmaceutical ingredients
(APIs) (ibuprofen (both the racemic compound (R/S) and S-enantiomer), fenbufen, flurbiprofen (R/S), ketoprofen (R/S), paracetamol,
piracetam, and salicylic acid) as part of a larger systematic study of synthon stability. From the screen, three new co-crystal systems
have been identified (ibuprofen (R/S and S) and salicylic acid) and their crystal structures determined. Because of poor crystal
growth synchrotron radiation was required for structure solution of the S-ibuprofen nicotinamide co-crystal. Two further potential
systems have also been discovered (fenbufen and flurbiprofen), but crystals suitable for structure determination have yet to be
obtained. A greater ability to control crystallization kinetics is required to yield phase-pure single-crystalline material for full verification
of this crystal engineering strategy.

In this work, the possibility of bottom-up creation of a relatively stable aqueous hydrocortisone nanosuspension
using microfluidic reactors was examined. The first part of the work involved a study of the
parameters of the microfluidic precipitation process that affect the size of generated drug particles.
These parameters included flow rates of drug solution and antisolvent, microfluidic channel diameters,
microreactors inlet angles and drug concentrations. The experimental results revealed that hydrocortisone
nano-sized dispersions in the range of 80¿450nm were obtained and the mean particle size could
be changed by modifying the experimental parameters and design of microreactors. The second part of
the work studied the possibility of preparing a hydrocortisone nanosuspension using microfluidic reactors.
The nano-sized particles generated from a microreactor were rapidly introduced into an aqueous
solution of stabilizers stirred at high speed with a propeller mixer. A tangential flow filtration system
was then used to concentrate the prepared nanosuspension. The nanosuspension produced was then
characterized using photon correlation spectroscopy (PCS), Zeta potential measurement, transmission
electron microscopy (TEM), differential scanning calorimetry (DSC) and X-ray analysis. Results showed
that a narrowsized nanosuspension composed of amorphous spherical particles with a mean particle size
of 500±64 nm, a polydispersity index of 0.21±0.026 and a zeta potential of ¿18±2.84mVwas obtained.
Physical stability studies showed that the hydrocortisone nanosuspension remained homogeneous with
slight increase in mean particle size and polydispersity index over a 3-month period.

The increasing prevalence of poorly soluble drugs in development provides notable risk of new products demonstrating low and erratic
bioavailabilty with consequences for safety and efficacy, particularly for drugs delivered by the oral route of administration. Although numerous
strategies exist for enhancing the bioavailability of drugs with low aqueous solubility, the success of these approaches is not yet able to be
guaranteed and is greatly dependent on the physical and chemical nature of the molecules being developed. Crystal engineering offers a number of
routes to improved solubility and dissolution rate, which can be adopted through an in-depth knowledge of crystallisation processes and the
molecular properties of active pharmaceutical ingredients. This article covers the concept and theory of crystal engineering and discusses the
potential benefits, disadvantages and methods of preparation of co-crystals, metastable polymorphs, high-energy amorphous forms and ultrafine
particles. Also considered within this review is the influence of crystallisation conditions on crystal habit and particle morphology with potential
implications for dissolution and oral absorption.

The formation of crystalline molecular complexes of benzoic acid and isonicotinamide with 1:1 and 2:1 compositions
has been investigated through solution cocrystallization. The 1:1 complex was solely obtained from ethanol solutions, while either
complex could be grown from aqueous and methanol solution by variation of the initial composition. The crystal structures of the
2:1 complex and a monohydrate of isonicotinamide were determined by single crystal X-ray diffraction. The intermolecular interactions
in the crystal structure of the complex were compared with other published carboxylic acid:isonicotinamide molecular complexes,
which highlights the robust nature of the acid · · · pyridine and acid · · · amide hydrogen bond, which exist in most cases. Complementary
computational studies into the binding of pairs of these molecules by ab initio calculations were found to support the experimental
observations and highlight the role of solvent in controlling the final crystalline form for multicomponent systems, through altering
the hierarchy of intermolecular interactions.

In this feature article we will focus on the issues relating to the crystal growth of co-crystals, with
a particular emphasis on drug development. The initial focus of this perspective is on the relevant
literature examples that may be able to inform our understanding with regards co-crystal
crystallisation and the allied supramolecular concepts. The second part of this perspective
contains selected examples from our own work, which add to the literature perspective. Topics
include; nucleation templates, in situ synchrotron XRD studies, solid-state synthesis through
mixing and screening strategies.

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